Establishing Standardized Biomedical Laboratory Technician Education for the Development of Biotech no logy Research in China

Chinese scientists have been actively engaged in biotechnology research since the mid-2Oth century.However,biotechnology education,especially biomedical laboratory technology education,is relatively scarce in China.More and more cutting-edge equipment and techniques have been introduced into biomedical laboratories in China,but there is a lack of high-quality techni&ans to apply these advancements to scientific research.In addition,the traditional education and apprenticeship systems have been demonstrated little progress.To address this gap,West China Hospital of Sichuan University established a 2-year educational program for laboratory technology in 2006 based on the residency training program.The project integrates scientific methods into the research laboratory technician training in relevant disciplines,and has developed a systematic,scientific,and effective standardized training system to cultivate high-level and stable experimental technician team for the need of advanced laboratories,which has been demonstrated gready improve the efficiency of biomedical researchers and laboratory facilities.In this article,we introduce the practical experience in establishment and development of a standardized training system for biomedical laboratory technicians to ensure the sustainable development of medical researches.

牛痘相关激酶2在神经发育过程中小胶质细胞介导的突触消除中起重要作用

在出生后的神经发育过程中,大脑神经回路的建立需要小胶质细胞消除过度的突触连接。小胶质细胞突触调节缺失已被证实与自闭症、精神分裂症和智力残疾等神经发育障碍有关。小胶质细胞中表达的牛痘相关激酶2(VRK2)可能可以激活突触消除的过程。在VRK2缺陷小鼠(VRK2KO)中,可以观察到小胶质细胞内突触前位点的减少。而且,在出生后第2周,VRK2KO小鼠的突触前位点和突出的数量都出现了异常增加。这些差异并没有持续到成年期。尽管突触数量的增加最终结局与正常小鼠无异,但成年VRK2KO小鼠在社交行为、情境恐惧记忆和空间记忆中表现出行为缺陷。

Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation

Lipid-coated perfluorocarbon nanodroplets(lp-NDs)hold great promise in bio-medicine as vehicles for drug delivery,molecular imaging and vaccine agents.However,their clinical utility is restricted by limited targeted accumulation,attributed to the innate immune system(IIS),which acts as the initial defense mechanism in humans.This study aimed to optimize lp-ND formulations to mini-mize non-specific clearance by the IIS.Ginsenosides(Gs),the principal components of Panax ginseng,possessing complement inhibition ability,structural similarity to cholesterol,and comparable fat solubi-lity to phospholipids,were used as promising candidate IIS inhibitors.Two different types of ginsenoside-based Ip-NDs(Gs Ip-NDs)were created,and their efficacy in reducing IS recognition was examined.The Gs p-NDs were observed to inhibit the adsorption of C3 in the protein corona(PC)and the generation of SC5b-9.Adding Gs to Ip-NDs reduced complement adsorption and phagocytosis,resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs.These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants,potentially reducing non-specific clear-ance by the IS and improving lifespan.

Enhancing sensitivity of triple-negative breast cancer to DNA-damaging therapy through chemical inhibition of the m6A methyltransferase METTL3

Dear Editor,N 6-methyladenosine(m^(6)A)is a critical mRNA modi-fication catalyzed by the enzyme methyltransferase-like 3(METTL3),with implications in RNA metabolism.METTL3 upregulation is associated with cancer progres-sion,metastasis,and drug resistance,making it a poten-tial therapeutic target[1].

Application of metabolomics in urolithiasis:the discovery and usage of succinate

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events.It has been shown that the occurrence of calcium oxalate monohydrate(COM)during stone formation is regulated by crystal growth modifiers.Although crystallization inhibitors have been recognized as a therapeutic modality for decades,limited progress has been made in the discovery of effective modifiers to intervene with stone disease.In this study,we have used metabolomics technologies,a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model.By in-depth mining and analysis of metabolomics data,we have screened five differential metabolites.Through density functional theory studies and bulk crystallization,we found that three of them(salicyluric,gentisic acid and succinate)could effectively inhibit nucleation in vitro.We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones.Notably,succinate,a key player in the tricarboxylic acid cycle,could decrease kidney calcium deposition and injury in the model.Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation,inhibition of cell adhesion and osteogenic differentiation.These findings indicated that succinate may provide a new therapeutic option for urinary stones.

FFAR4 improves the senescence of tubular epithelial cells by AMPK/SirT3 signaling in acute kidney injury

Acute kidney injury(AKI)is a serious clinical complication with high morbidity and mortality rates.Despite substantial progress in understanding the mechanism of AKI,no effective therapy is available for treatment or prevention.We previously found that G protein-coupled receptor(GPCR)family member free fatty acid receptor 4(FFAR4)agonist TUG891 alleviated kidney dysfunction and tubular injury in AKI mice.However,the versatile role of FFAR4 in kidney has not been well characterized.In the study,the expression of FFAR4 was abnormally decreased in tubular epithelial cells(TECs)of cisplatin,cecal ligation/perforation and ischemia/reperfusion injury-induced AKI mice,respectively.Systemic and conditional TEC-specific knockout of FFAR4 aggravated renal function and pathological damage,whereas FFAR4 activation by TUG-891 alleviated the severity of disease in cisplatin-induced AKI mice.Notably,FFAR4,as a key determinant,was firstly explored to regulate cellular senescence both in injured kidneys of AKI mice and TECs,which was indicated by senescence-associatedβ-galactosidase(SA-β-gal)activity,marker protein p53,p21,Lamin B1,phospho-histone H2A.X,phospho-Rb expression,and secretory phenotype IL-6 level.Mechanistically,pharmacological activation and overexpression of FFAR4 reversed the decrease of aging-related SirT3 protein,where FFAR4 regulated SirT3 expression to exhibit anti-senescent effect via Gq subunit-mediated CaMKKβ/AMPK signaling in cisplatin-induced mice and TECs.These findings highlight the original role of tubular FFAR4 in cellular senescence via AMPK/SirT3 signaling and identify FFAR4 as a potential drug target against AKI.

Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues,which has many side effects.Biomaterials such as small intestine submucosa(SIS)can provide an alternative scaffold for the repair as bladder patches.Previous studies have shown that SIS could enhance the capacity and compliance of the bladder,but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS.Procyanidins(PC),a natural bio-crosslinking agent,has shown anti-calcification,anti-inflammatory and anti-oxidation properties.More importantly,PC and SIS can crosslink through hydrogen bonds,which may endow the material with enhanced mechanical property and stabilized functionalities.In this study,various concentrations of PC-crosslinked SIS(PC-SIS)were prepared to repair the full-thickness bladder defects,with an aim to reduce complications and enhance bladder functions.In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property,ability to promote smooth muscle cell adhesion and upregulate functional genes expression.Using a rabbit model with bladder defects,we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration,in particular smooth muscle remodeling and improvement of urinary functions.The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.

Accelerating ESD-induced gastric ulcer healing using a pH-responsive polyurethane/small intestinal submucosa hydrogel delivered by endoscopic catheter

Endoscopic submucosal dissection(ESD)is the standard treatment for early-stage gastric cancer,but the large post-operative ulcers caused by ESD often lead to serious side effects.Post-ESD mu-cosal repair materials provide a new option for the treatment of post-ESD ulcers.In this study,we developed a polyurethane/small intestinal submucosa(PU/SIS)hydrogel and investigated its effi-cacy for accelerating ESD-induced ulcer healing in a canine model.PU/SIS hydrogel possessed great biocompatibility and distinctive pH-sensitive swelling properties and protected GES-1 cells from acid attack through forming a dense film in acidic conditions in vitro.Besides,PU/SIS gels present a strong bio-adhesion to gastric tissues under acidic conditions,thus ensuring the reten-tion time of PU/SIS gels in vivo.In a canine model,PU/SIS hydrogel was easily delivered via endoscopy and adhered to the ulcer sites.PU/SIS hydrogel accelerated gastric ulcer healing at an early stage with more epithelium regeneration and slight inflammation.Our findings reveal PU/SIS hydrogel is a promising and attractive candidate for ESD-induced ulcer repair.

Single-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis

The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer.However,cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogenesis in colorectal tissues.Here,we performed a single-cell RNA sequencing survey of 54,788 cells from patient-matched tissue samples,including blood,normal tissue,para-cancer,polyp,and colorectal cancer.

Promotion of right ventricular outflow tract reconstruction using a novel cardiac patch incorporated with hypoxia-pretreated urine-derived stem cells

Approximately 25%of patients with congenital heart disease require implantation of patches to repair.However,most of the currently available patches are made of inert materials with unmatched electrical conductivity and mechanical properties,which may lead to an increased risk for arrhythmia and heart failure.In this study,we have developed a novel Polyurethane/Small intestinal submucosa patch(PSP)with mechanical and electrical properties similar to those of the native myocardial tissue,and assessed its feasibility for the reconstruction of right ventricular outflow tract.A right ventricular outflow tract reconstruction model was constructed in 40 rabbits.Compared with commercially available bovine pericardium patch,the PSP patch has shown better histocompatibility and biodegradability,in addition with significantly improved cardiac function.To tackle the significant fibrosis and relatively poor vascularization during tissue remodeling,we have further developed a bioactive patch by incorporating the PSP composites with urine-derived stem cells(USCs)which were pretreated with hypoxia.The results showed that the hypoxia-pretreated bioactive patch could significantly inhibit fibrosis and promote vascularization and muscularization,resulting in better right heart function.Our findings suggested that the PSP patch combined with hypoxia-pretreated USCs may provide a better strategy for the treatment of congenital heart disease.

Application of antibody-conjugated small intestine submucosa to capture urine-derived stem cells for bladder repair in a rabbit model

The need for bladder reconstruction and side effects of cystoplasty have spawned the demand for the development of alternative material substitutes.Biomaterials such as submucosa of small intestine(SIS)have been widely used as patches for bladder repair,but the outcomes are not fully satisfactory.To capture stem cells in situ has been considered as a promising strategy to speed up the process of re-cellularization and functionalization.In this study,we have developed an anti-CD29 antibody-conjugated SIS scaffold(AC-SIS)which is capable of specifically capturing urine-derived stem cells(USCs)in situ for tissue repair and regeneration.The scaffold has exhibited effective capture capacity and sound biocompatibility.In vivo experiment proved that the AC-SIS scaffold could promote rapid endothelium healing and smooth muscle regeneration.The endogenous stem cell capturing scaffolds has thereby provided a new revenue for developing effective and safer bladder patches.

High-throughput screening and evaluation of repurposed drugs targeting the SARS-CoV-2 main protease

Dear editor,To date,a number of clinically approved drugs have been evaluated for potential to treat coronavirus disease 2019(COVID-19),such as lopinavir/ritonavir,hydroxychloroquine,cobicistat,and darunavir.Some of these drugs have been proven to be effective in vitro;however,clinical trials showed that none of these compounds led to a significant improvement in symptoms or length of hospitalization.Thus,it is essential and more reliable to start from a defined target to ide ntify can didate drugs.

Inhibition of xanthine oxidase alleviated pancreatic necrosis via HIF-1α-regulated LDHA and NLRP3 signaling pathway in acute pancreatitis

Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment options.Although inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical trials,whether XO is a target of AP and what its the main mechanism of action is remains unclear.Here,we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP.We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models.We also found that allopurinol and febuxostat,as purine-like and non-purine XO inhibitors,respectively,exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points.Moreover,we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity.Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha(HIF-1α)-regulated lactate dehydrogenase A(LDHA)and NOD-like receptor family pyrin domain containing 3(NLRP3)signaling pathways and reduced the enrichment of^(13)C_(6)-glucose to^(13)C_(3)-lactate.Lastly,we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels,while pancreatic XO and urate were also increased in severe AP patients.These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.